Virus structure determination using electron microscopy has become a useful research tool aimed at understanding viral assembly and infectivity to facilitate the design of anti-viral drugs and virus-based gene delivery systems. Our long term goal is to broaden the group of people able to determine virus structures by providing an integrated software suite for three-dimensional virus structure determination using electron microscopy. The software suite, called Tumbleweed, will allow easy, efficient, and routine determination of icosahedral virus structures from electron micrographs. Novel aspects of Tumbleweed will include a comprehensive suite of tools for icosahedral structure determination, incorporation of an expert system to guide users through the reconstruction procedure, and data analysis tools to ensure that structures are determined accurately. Tumbleweed will also provide a consistent easy to use graphical user interface to all reconstruction tools including data analysis, data management, and data logging. In addition, Tumbleweed will provide tools for image selection, quality assessment, and structure visualization that can be used with any electron microscopy structure determination method. Thus, in addition to virologists, target users include electron microscopists and structural biologists. The result of this Phase Il SBIR will be a completely integrated and tested software package allowing easy, efficient, and routine virus structure determination. PROPOSED COMMERCIAL APPLICATIONS: Tumbleweed is targeted at a large group of users with varied knowledge, experience, and research goals. Virologists will be attracted to the extensive user guidance and intuitive design. Structural biologists and electron microscopists performing virus structure determination will be attracted to the concept of a complete integrated software package. Last, all electron microscopists and structural biologists will be attracted to the integration of all general data processing into a single extendible package. Combined this group should provide a large user-base allowing QED Labs to commercialize Tumbleweed successfully.